Field of the Invention
The invention relates to substituted N-(2-piperidylmethyl)benzamides which are pharmaceutically active. More specifically, the invention relates to such compounds which exhibit antiarrhythmic activity. Pharmaceutical compositions comprising and pharmacological methods for using such compounds are also described.
Description of the Related Art
Certain substituted N-(2-piperidylmethyl) benzamides are known antiarrhythmic agents. Notable among these are the various mono-, bis- and tris-(2,2,2-trifluoroethoxy)-N-(2-piperidylmethyl)benzamides most notably the compound 2,5-bis(2,2,2-trifluoroethoxy)-N-(2-piperidylmethyl)benzamide acetate, which is an antiarrhythmic drug sold under the trade designation Tambocor.RTM. brand flecainide acetate, disclosed in U.S. Pat. No. 3,900,481. Related to these compounds are the tertiary benzamides disclosed in U.S. Pat. No. 4,097,481 which also exhibit antiarrhythmic activity.
Disclosed in U.S. Pat. No. 4,339,587 is the antiarrhythmic compound 5-hydroxy-N-(2-piperidylmethyl)-2-(2,2,2-trifluoroethoxy)benzamide. Also disclosed is 5-hydroxy-N-(2-pyridylmethyl)-2-(2,2,2-trifluoroethoxy)benzamide, a precursor to the above-mentioned piperidyl analog and an intermediate in a synthesis of flecainide disclosed in U.S. Pat. No. 3,900,481. This compound also serves as an intermediate in the preparation of some of the compounds of the present invention.
Last, many of the compounds disclosed in the patents mentioned above are also disclosed in J. Med. Chem. 1977, 20, 821. Also described therein are several 2-(2,2,2-trifluoroethoxy)-N-(2-piperidylmethyl)benzamides in which the aryl ring is substituted in the 5-position by methyl, chloro, or fluoro. These latter compounds are said to possess substantially reduced antiarrhythmic activity as compared to the corresponding 5-(2,2,2-trifluoroethoxy) compound.